While evidence suggests that plasmid encoded proteins are key in understanding the host-pathogen interaction in Borrelia infections, the functions for most of these proteins remain undefined. Since the plasmid carried genes are largely unique to the Borrelia, it is likely that they hold the key to understanding the unique attributes of Borrelia biology and pathogenesis. The bdr gene family is a large, polymorphic, plasmid carried gene family carried and expressed by all species of the genus. In Borrelia burgdorferi B31MI the gene family contains 18 members distributed among the linear and circular plasmids. We have demonstrated that the Bdr proteins are organized into distinct sub-families, are associated with the inner membrane, and are differentially expressed in response to environmental conditions. In this application we present a strategy for defining the expression patterns of the Bdr proteins in different environments, elucidating the mechanisms involved in their regulation, and for testing the effects of Bdr gene inactivation on Borrelia pathogenesis.